The First Hes1 Dimer Inhibitors from Natural Products

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2009 Sep 1

PMID 19716294

Citations 8

Authors

Midori A Arai

Ayako Masada

Toshiyuki Ohtsuka

Ryoichiro Kageyama

Masami Ishibashi

Affiliations

Soon will be listed here.

Abstract

In the present study, we developed a high-throughput screening system for small molecule-inhibitors of the basic helix-loop-helix (bHLH) transcriptional repressor factor Hes1. Successful dimerization of Hes1 immobilized on a microplate and fluorophore (Cy3)-labelled Hes1 was confirmed. Using this system, several natural products were identified as the first Hes1 dimer inhibitors. Of these, two compounds which were isolated from myxomycetes (true slime molds) inhibited Hes1 from N box-dependent suppression of the gene expression in C3H10T1/2 cells.

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Total synthesis of lindbladione, a Hes1 dimerization inhibitor and neural stem cell activator isolated from Lindbladia tubulina.

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Small-molecule screening yields a compound that inhibits the cancer-associated transcription factor Hes1 via the PHB2 chaperone.

Perron A, Nishikawa Y, Iwata J, Shimojo H, Takaya J, Kobayashi K J Biol Chem. 2018; 293(21):8285-8294.

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